| Literature DB >> 16503142 |
Darren McKerrecher1, Joanne V Allen, Peter W R Caulkett, Craig S Donald, Mark L Fenwick, Emma Grange, Keith M Johnson, Craig Johnstone, Clifford D Jones, Kurt G Pike, John W Rayner, Rolf P Walker.
Abstract
The optimisation of a series of glucokinase activators is described, including attempts to uncouple the relationship between potency and plasma protein binding, and to better understand the key pharmacokinetic properties of the series. The use of unbound clearance as an optimisation parameter facilitated the identification of GKA50, a compound which combines excellent potency and pharmacokinetics with good free drug levels and solubility, and exhibits in vivo efficacy at 1mg/kg po in an acute rat OGTT model.Entities:
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Year: 2006 PMID： 16503142 DOI： 10.1016/j.bmcl.2006.02.022
Source DB: PubMed Journal: Bioorg Med Chem Lett ISSN： 0960-894X Impact factor: 2.823